Bone marrow and stem cell transplantation is being used for an increasing number of procedures that are performed on patients undergoing chemo- or radiotherapy. This procedure can be simplified, made more cost effective and reliable if hematopoietic stem, progenitor and precursor cells could be expanded greatly in number from a small aspirate. During Phase I of this program, a prototype perfusion bioreactor system was developed that enables the expansion of bone marrow cells from adult donors as well as hematopoietic cells obtained from mobilized peripheral blood and umbilical cord blood. Bone marrow cell populations expand by a factor of 8 and 10 while their progenitor cell content increased by a factor of 10 to 30 and the number of long- term culture initiating cells increased by 4 to 10 fold. The objectives of the proposed Phase II program are: 1. Define the material composition and characteristics of the cell growth surfaces, and techniques for large volume manufacturing; 2. Optimize oxygen delivery and other operating conditions necessary for the production of human stem and hematopoietic progenitor cells using cell culture chambers; 3. Design, build and test a clinical size unit based on the parameters defined using the small scale units; and 4. Evaluate cell growth reliability of the cell culture chambers and define the expansion characteristics of patient and normal donor marrow in this system. Successful completion of this program will lead to clinical trials to determine the efficacy of expanded hematopoietic cell populations.
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